1. Field of the Invention
The present invention relates to a process for preparing optically active 1-substituted-3-hydroxybutane or its ester derivatives, and, more particularly, to a process for preparing optically active 1-substituted-3-hydroxybutane or its ester derivatives which comprises treating racemic 1-substituted-3-hydroxybutane or its ester derivatives with a lipase.
The products of the present invention can be used, for example as a raw material of azetidinone compounds disclosed in Japanese patent application laid-open No. 207373/1986.
2. Description of the Background Art
(3S, 4R)-4-phenylthio-3-[(R)-1-tert-butyldimethyl-sililoxyethyl]-azetidine-2-on e and (3S, 4R)-4-acetoxy-3-[(R)-1-tert-butyldimethylsililoxyethyl]- azetidine-2-one are useful compounds as raw materials for the synthesis of penems or carbapenems which are antibiotics. Since these antibiotics are attracting a great deal of attention in recent years and their development are energetically undertaken, the need for the abundant availability of raw materials is increasing.
Although the process of manufacturing (3S, 4R)-4-phenylthio-3-[(R)-1-tert-butyldimethylsililoxyethyl]-azetidine-2-one disclosed in Japanese patent application laid-open No. 207373/1986 may be a useful method, actual practice of the process requires abundant and inexpensive availability of optically active 1,3-butanediol or its derivatives which are the raw materials of the process.
A method of reducing optically active 3-hydroxylbutyric acid derivatives with a hydrogenated metallic reducing agent, a method of reducing 3-oxobutanol with an asymmetric reducing agent, a method of fractionating 1,3-butandiol derivatives with a fractionator, and the like are known as processes for manufacturing optically active 1,3-butanediol. All these methods, however, have problems in the costs of reducing agents or fractionating agents, processability of the reactions, yields, optical purity of the products, and the like, when they are applied to a large scale production. Since none of the processes are practically useful, development of a new process is desired.
In view of this situation, the present inventors have undertaken extensive studies, and have found that an optically active 1-substituted-3-hydroxybutane or its derivative represented by formula (II) or (III), ##STR3## could be prepared in a high yield and in high optical purity by a simple process in which an ester derivative of racemic 1-substituted-3-hydroxybutane of formula (I), ##STR4## is treated with a lipase to effect asymmetric hydrolysis.
In the above formulae (I) to (III), R.sub.1 is an alkyl group having 1-8 carbon atoms, an aryl group having 6-10 carbon atoms, an alkoxy group having 1-6 carbon atoms, or an aryloxy group having 6-10 carbon atoms, wherein hydrogen atoms on the carbon atoms of the alkyl, aryl, or alkoxy group may optionally be substituted by alkyl, aryl, hydroxyl, alkoxy, alkylthio, or arylthio group, and R.sub.2 is a halogen atom, an alkylsulfonyloxy group having 1-8 carbon atoms, an arylsulfonyloxy group having 6-10 carbon atoms, an alkylthio group having 1-8 carbon atoms, or an arylthio group having 6-10 carbon atoms, wherein hydrogen atoms on the carbon atoms of the alkylsulfonyloxy, arylsulfonyloxy, alkylthio, or the arylthio group may optionally be substituted by halogen, alkyl, aryl, hydroxyl, or alkoxy group, and in formulae (II) and (III) the secondary hydroxyl group has either R or S configuration.